The purpose of this proposal is to acquire a 600 MHz nuclear magnetic resonance (NMR) spectrometer capable of structural analysis of large biological macromolecules. Researchers from the Department of Biochemistry, Molecular Biology and Cell Biology, the Department of Chemistry and the Medical School have formed a structural biology research program for which this proposal will provide a crucial piece of instrumentation support. Already in place for this structural biology initiative are three x-ray crystallographers equipped with a Rigaku x-ray generator, two Nicolet area detectors and associated graphics, and computer facilities. In addition the National Institutes of Health has recently funded a pulsed ENDOR-EPR facility. Thus, the acquisition of a 600 MHz NMR spectrometer will complete the core instrumentation required for the development of a premier structural biology research program. The research to be supported by the requested high field NMR instrument is centered in five areas. These are : (1) Structure, mechanism and dynamics of proteins; (2) Respiratory proteins and photosynthesis; (3) Complexes with DNA and enzyme inhibitors; (4) Antitumor agents and carcinogenesis; (5) Membrane signaling and receptors. None of these projects can be satisfactorily addressed with the 400 MHz NMR spectrometer presently at Northwestern. Several of the projects involve detailed structural analysis of proteins and protein-nucleic acid complexes which are significantly larger than those which have been carried out to date. To study these more complex systems, the user group will extensively employ their expertise in isotopic labeling. The wide range of systems to be studied promise to make optimal use of the benefits of the increased dispersion and sensitivity that the 600 MHz spectrometer provides. The establishment of techniques for the analysis of biomacromolecules as large as 40 kD will have a scientific impact well beyond the particular systems described herein.